Myeloid-like tumor hybrid cells in bone marrow promote progression of prostate cancer bone metastasis.
Myeloid-like tumor hybrid cells in bone marrow promote progression of prostate cancer bone metastasis.
复制标题
骨髓中的髓系样肿瘤杂交细胞促进前列腺癌骨转移的进展。
DOI：
10.1186/s13045-023-01442-4
复制
发表时间：
2023-05-03
影响因子：
28.5
通讯作者：
中科院分区：
文献类型：
--
作者：
骨转移是前列腺癌（PCa）患者死亡的主要原因，目前尚无有效的治疗方法。骨髓中播散的肿瘤细胞常获得新的特性，导致治疗耐药和肿瘤复发。因此，了解骨髓中播散性前列腺癌细胞的状态对于开发新的治疗方法至关重要。我们从PCa骨转移的单细胞RNA测序数据分析了播散性肿瘤细胞的转录组。通过尾动脉注射肿瘤细胞建立骨转移模型，并采用流式细胞仪分选肿瘤杂交细胞。我们进行了多组学分析，包括转录组学，蛋白质组学和磷酸化蛋白质组学分析，以比较肿瘤杂交细胞和亲本细胞之间的差异。体内实验分析了杂交细胞的肿瘤生长速率、转移和致瘤潜力、药物和辐射敏感性。进行单细胞RNA测序和CyTOF以分析杂交细胞对肿瘤微环境的影响。在这里，我们在PCa骨转移中发现了一个独特的癌细胞簇，它表达髓样细胞标志物，并显示出与免疫调节和肿瘤进展相关的途径的显著变化。我们发现播散性肿瘤细胞与骨髓细胞的融合可能是这些髓样肿瘤细胞的来源。多组学分析显示，与细胞粘附和增殖相关的细胞粘附、紧密连接、DNA复制和细胞周期等通路在这些杂交细胞中发生了显著改变。体内实验表明，杂交细胞的增殖率明显提高，并具有转移潜能。单细胞RNA测序和CyTOF显示，肿瘤相关中性粒细胞/单核细胞/巨噬细胞高度富集在杂交细胞诱导的肿瘤微环境中，具有更高的免疫抑制能力。另外，杂交细胞表现出增强的EMT表型，具有更高的致瘤性，并且对多西他赛和铁凋亡具有抗性，但对放射治疗敏感。总之，我们的数据表明，骨髓中自发的细胞融合可以产生骨髓样肿瘤杂交细胞，促进骨转移的进展，这些独特的播散性肿瘤细胞群可以为PCa骨转移提供潜在的治疗靶点。在线版本包含补充材料，可通过10.1186/s13045-023-01442-4获得。
Bone metastasis is the leading cause of death in patients with prostate cancer (PCa) and currently has no effective treatment. Disseminated tumor cells in bone marrow often obtain new characteristics to cause therapy resistance and tumor recurrence. Thus, understanding the status of disseminated prostate cancer cells in bone marrow is crucial for developing a new treatment. We analyzed the transcriptome of disseminated tumor cells from a single cell RNA-sequencing data of PCa bone metastases. We built a bone metastasis model through caudal artery injection of tumor cells, and sorted the tumor hybrid cells by flow cytometry. We performed multi-omics analysis, including transcriptomic, proteomic and phosphoproteomic analysis, to compare the difference between the tumor hybrid cells and parental cells. In vivo experiments were performed to analyze the tumor growth rate, metastatic and tumorigenic potential, drug and radiation sensitivity in hybrid cells. Single cell RNA-sequencing and CyTOF were performed to analyze the impact of hybrid cells on tumor microenvironment. Here, we identified a unique cluster of cancer cells in PCa bone metastases, which expressed myeloid cell markers and showed a significant change in pathways related to immune regulation and tumor progression. We found that cell fusion between disseminated tumor cells and bone marrow cells can be source of these myeloid-like tumor cells. Multi-omics showed the pathways related to cell adhesion and proliferation, such as focal adhesion, tight junction, DNA replication, and cell cycle, were most significantly changed in these hybrid cells. In vivo experiment showed hybrid cells had a significantly increased proliferative rate, and metastatic potential. Single cell RNA-sequencing and CyTOF showed tumor-associated neutrophils/monocytes/macrophages were highly enriched in hybrid cells-induced tumor microenvironment with a higher immunosuppressive capacity. Otherwise, the hybrid cells showed an enhanced EMT phenotype with higher tumorigenicity, and were resistant to docetaxel and ferroptosis, but sensitive to radiotherapy. Taken together, our data demonstrate that spontaneous cell fusion in bone marrow can generate myeloid-like tumor hybrid cells that promote the progression of bone metastasis, and these unique population of disseminated tumor cells can provide a potential therapeutic target for PCa bone metastasis. The online version contains supplementary material available at 10.1186/s13045-023-01442-4.
登录
查看更多内容
影响因子：
10.9
作者：
Dong B;Li S;Zhu S;Yi M;Luo S;Wu K
通讯作者：
Wu K
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
具有高度异常基因组的传播肿瘤细胞与可手术食管腺癌的预后不良有关。
影响因子：
8.8
作者：
Schumacher S;Bartenhagen C;Hoffmann M;Will D;Fischer JC;Baldus SE;Vay C;Fluegen G;Dizdar L;Vallböhmer D;Klein CA;Knoefel WT;Stoecklein NH;Möhlendick B
通讯作者：
Möhlendick B
影响因子：
10.9
作者：
Chen, Erbao;He, Yu;Jiang, Jing;Yi, Jing;Zou, Zhilin;Song, Qiuzi;Ren, Qingqi;Lin, Zewei;Lu, Yi;Liu, Jikui;Zhang, Jian
通讯作者：
Zhang, Jian
影响因子：
13.6
作者：
Gast CE;Silk AD;Zarour L;Riegler L;Burkhart JG;Gustafson KT;Parappilly MS;Roh-Johnson M;Goodman JR;Olson B;Schmidt M;Swain JR;Davies PS;Shasthri V;Iizuka S;Flynn P;Watson S;Korkola J;Courtneidge SA;Fischer JM;Jaboin J;Billingsley KG;Lopez CD;Burchard J;Gray J;Coussens LM;Sheppard BC;Wong MH
通讯作者：
Wong MH